Safety of intrathecal injection of Wharton's jellyderived mesenchymal stem cells in amyotrophic lateral sclerosis therapy

Animal experiments have confirmed that mesenchymal stem cells can inhibit motor neuron apoptosis and inflammatory factor expression and increase neurotrophic factor expression. Therefore, mesenchymal stem cells have been shown to exhibit prospects in the treatment of amyotrophic lateral sclerosis. However, the safety of their clinical application needs to be validated. To investigate the safety of intrathecal injection of Wharton's jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy, 43 patients(16 females and 27 males, mean age of 57.3 years) received an average dose of 0.42 × 106 cells/kg through intrathecal administration at the cervical, thoracic or lumbar region depending on the clinical symptoms. There was a 2 month interval between two injections. The adverse events occurring during a 6-month treatment period were evaluated. No adverse events occurred. Headache occurred in one case only after first injection of stem cells. This suggests that intrathecal injection of Wharton's Jelly-derived mesenchymal stem cells is well tolerated in patients with amyotrophic lateral sclerosis. This study was approved by the Bioethical Committee of School of Medicine, University of Warmia and Mazury in Olsztyn, Poland(approval No. 36/2014 and approval No. 8/2016). This study was registered with the ClinicalTrials.gov(identifier: NCT02881476)on August 29, 2016.

Numerical Simulation of Asphaltene Precipitation and Deposition during Natural Gas and CO_(2) Injection

Asphaltene deposition is a significant problem during gas injection processes,as it can block the porous medium,the wellbore,and the involved facilities,significantly impacting reservoir productivity and ultimate oil recovery.Only a few studies have investigated the numerical modeling of this potential effect in porous media.This study focuses on asphaltene deposition due to natural gas and CO_(2) injection.Predictions of the effect of gas injection on asphaltene deposition behavior have been made using a 3D numerical simulation model.The results indicate that the injection of natural gas exacerbates asphaltene deposition,leading to a significant reduction in permeability near the injection well and throughout the reservoir.This reduction in permeability strongly affects the ability of gas toflow through the reservoir,resulting in an improvement of the displacement front.The displacement effi-ciency of the injection gas process increases by up to 1.40%when gas is injected at 5500 psi,compared to the scenario where the asphaltene model is not considered.CO_(2) injection leads to a miscible process with crude oil,extracting light and intermediate components,which intensifies asphaltene precipitation and increases the viscosity of the remaining crude oil,ultimately reducing the recovery rate.

A Comparative Study of Intrathecal Injection of Bupivacaine Alone or with Fentanyl, Clonidine, and Neostigmine in Lower Abdominal Surgeries

Background: Anesthesiologists are responsible for the development of pain services in the current era. Hence ideal adjuvants that can be used with bupivacaine for stable intraoperative conditions and prolonging the postoperative analgesia with fewer side effects are being investigated. Opioids, despite useful as adjuvants, are associated with undesirable side effects. Aim of the work: The study was done to compare analgesic efficacy and hemodynamic of intrathecal injection of bupivacaine alone or with fentanyl, clonidine, and neostigmine in lower abdominal surgeries, over the first 24 postoperative hours, in a randomized, double-blind, and clinical trial. Methods: 100 Patients were randomized into four equal groups, 25 patients in each group;Group B patients received 2.5 ml of 0.5% hyperbaric bupivacaine and 0.5 ml of normal saline. Group BF patients received 2.5 ml of 0.5% hyperbaric bupivacaine with (25 mics) of fentanyl. Group BC patients received 2.5 ml of 0.5% hyperbaric bupivacaine with 0.5 ml (75 mics) of clonidine. Group BN patients received 2.5 ml of 0.5% hyperbaric bupivacaine with 0.1 ml of neostigmine (50 mics) and 0.4 ml of normal saline. Intrathecal anesthesia was done with a recording of parameters intraoperative and the post-operative period. Each patient was assessed for hemodynamic parameters and effective analgesia in operation, and presence of complications (nausea, vomiting, sedation and pruritus) visual analogue pain score (VAS) postoperatively by a blinded investigator in the post-anesthesia care unit (PACU) and at 1, 2, 3, 4, 8 12, 18 and 24 h postoperatively. Results: The postoperative analgesia is more effective with group BC (the gold standard) than group B, group BF, and group BN. As regard complications during the study in all groups, complications as nausea, and vomiting were mainly with group BN;hypotension was primarily in group BC. Conclusion: Bupivacaine clonidine, bupivacaine neostigmine, and bupivacaine fentanyl intrathecal anesthesia produced a longer duration of postoperative analgesia after lower abdominal surgery in patients than bupivacaine alone. Bupivacaine clonidine mixture had the most extended period of analgesia, but with hypotension. So bupivacaine fentanyl mixture with moderate duration of analgesia and minimal side effects is most safe for a patient.

A Probabilistic Trust Model and Control Algorithm to Protect 6G Networks against Malicious Data Injection Attacks in Edge Computing Environments

Future 6G communications are envisioned to enable a large catalogue of pioneering applications.These will range from networked Cyber-Physical Systems to edge computing devices,establishing real-time feedback control loops critical for managing Industry 5.0 deployments,digital agriculture systems,and essential infrastructures.The provision of extensive machine-type communications through 6G will render many of these innovative systems autonomous and unsupervised.While full automation will enhance industrial efficiency significantly,it concurrently introduces new cyber risks and vulnerabilities.In particular,unattended systems are highly susceptible to trust issues:malicious nodes and false information can be easily introduced into control loops.Additionally,Denialof-Service attacks can be executed by inundating the network with valueless noise.Current anomaly detection schemes require the entire transformation of the control software to integrate new steps and can only mitigate anomalies that conform to predefined mathematical models.Solutions based on an exhaustive data collection to detect anomalies are precise but extremely slow.Standard models,with their limited understanding of mobile networks,can achieve precision rates no higher than 75%.Therefore,more general and transversal protection mechanisms are needed to detect malicious behaviors transparently.This paper introduces a probabilistic trust model and control algorithm designed to address this gap.The model determines the probability of any node to be trustworthy.Communication channels are pruned for those nodes whose probability is below a given threshold.The trust control algorithmcomprises three primary phases,which feed themodel with three different probabilities,which are weighted and combined.Initially,anomalous nodes are identified using Gaussian mixture models and clustering technologies.Next,traffic patterns are studied using digital Bessel functions and the functional scalar product.Finally,the information coherence and content are analyzed.The noise content and abnormal information sequences are detected using a Volterra filter and a bank of Finite Impulse Response filters.An experimental validation based on simulation tools and environments was carried out.Results show the proposed solution can successfully detect up to 92%of malicious data injection attacks.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

Personalized laparoscopic radical resection of gallbladder cancer by staining of the liver draining area through ICG injection into the cholecystic artery

Gallbladder cancer(GBC)is a common malignant tumor often diagnosed in advanced stages.Surgery is among the most important treatments for GBC.Radical resection of GBC involves removal of the gallbladder and the gallbladder bed[liver segments(S)4b and 5],and hepatoduodenal ligament regional lymphadenectomy.The main GBC metastasis modes are blood and lymph node metastases.The scope of resection/wedge resection or regular S4b and S5 hepatectomy for blood metastasis is a matter of debate.A variety of hepatectomy methods have been proposed for T2 stage GBC,but no consensus has been reached regarding the scope of radical resection.Currently,the liver resection range is determined by branches of the portal vein.S4b and S5 hepatectomy is determined according to the liver portal vein branch perfusion area,but the rationale for liver resection for GBC is to eliminate potential metastasis from the cystic vein reflux area to the liver.In the case described herein,we used a novel technique and theoretical framework to conduct laparoscopic radical resection of gallbladder cancer(LRRGC)facilitated by staining of the liver draining area with an indocyanine green(ICG)injection into the cholecystic artery.

Treatment of SMA type 1 infants using a single-dose AAV9-mediated gene therapy via intrathecal injection of GC101:An open-label,single-arm study

Spinal muscular atrophy(SMA),a neurodegenerative disorder caused by mutations in survival motor neuron 1(SMN1)resulting in reduced expression of the survival motor neuron(SMN)protein,is inherited in an autosomal recessive manner.SMA type 1 is the most frequent subtype of SMA characterized by onset before 6 months of life,inability to achieve independent sitting,and rapidly progressive respiratory and bulbar deterioration,causing a mortality of>90%before 2 years of age.[1]Currently,there have been two lifelong splice-modifying therapies(nusinersen and risdiplam),and a single-dose gene replacement therapy via intravenous onasemnogene abeparvovec for SMA type 1 patients.

Does HSP27 injection induce glaucoma damage in mice?

In a further aging society,excellent eyesight is an integral part of overall well-being and quality of life.Preserving good vision is crucial to maintaining mobility,independence,and mental health.There can be several reasons for visual impairment in elderly people,these include age-related macular degeneration,the leading cause of vision loss among older adults,cataract,glaucoma,diabetic retinopathy,retinal detachment,and others.

Tofacitinib combined with local low-dose ixekizumab injection benefits those with peripheral psoriatic arthritis

Dear Editor,Treating psoriatic arthritis(PsA)is always difficult.Systemic treatments can be administered either orally or through intramuscular and intra-articular injection,including conventional synthetics,biologics and targeted synthetic disease-modifying antirheumatic drugs[1].The alternatives,topical external therapies,are not effective on joint lesions due to drug permeability issues.Drugs injected into the articular cavity are also unsuitable for small peripheral joint lesions,the most common manifestations of PsA.The limited treatment options for PsA present a challenge.

Comparative study of boron and neon injections on divertor heat fluxes using SOLPS-ITER simulations

Based on the EAST equilibrium,the effects of boron(B)and neon(Ne)injected at different locations on the target heat load,and the distributions of B and Ne particles were investigated by transport code SOLPS-ITER.It was found that the B injection was more sensitive to the injection location for heat flux control than impurity Ne.The high electron and ion densities near the inner target in the discharge with impurity B injected from over X-point(R1)led to plasma detachment only at the inner target,and the localized B ions in the cases with injection from outer target location(R2)and upstream location(R3)led to far-SOL detachment at the outer target,but not at the inner target.In contrast,for Ne,the spatial distributions of Ne ions and electrons were found to be similar in all the cases at the three injection locations,and the detached plasma was achieved at the inner target and the electron temperature was reduced at the outer target.For locations R2 and R3,impurity B showed a more pronounced effect on the heat flux at the far-SOL of the outer target.Further analysis indicated that Ne atoms came mainly from the recycling sources,whereas B atoms came mainly from injection,and that their distinct atomic distributions resulted from the difference in the ionization threshold and ionization mean free path.In addition,the radiation proportion of B in the divertor region was larger than that of Ne when the total radiation power was similar,which suggests that B has less influence on the core region.

Experimental study of the influencing factors and mechanisms of the pressure-reduction and augmented injection effect by nanoparticles in ultra-low permeability reservoirs

Nanoparticles(NPs)have gained significant attention as a functional material due to their ability to effectively enhance pressure reduction in injection processes in ultra-low permeability reservoirs.NPs are typically studied in controlled laboratory conditions,and their behavior in real-world,complex environments such as ultra-low permeability reservoirs,is not well understood due to the limited scope of their applications.This study investigates the efficacy and underlying mechanisms of NPs in decreasing injection pressure under various injection conditions(25—85℃,10—25 MPa).The results reveal that under optimal injection conditions,NPs effectively reduce injection pressure by a maximum of 22.77%in core experiment.The pressure reduction rate is found to be positively correlated with oil saturation and permeability,and negatively correlated with temperature and salinity.Furthermore,particle image velocimetry(PIV)experiments(25℃,atmospheric pressure)indicate that the pressure reduction is achieved by NPs through the reduction of wall shear resistance and wettability change.This work has important implications for the design of water injection strategies in ultra-low permeability reservoirs.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

Oxygen variation in titanium powder and metal injection molding

The control of oxygen is paramount in achieving high-performance titanium(Ti)parts by powder metallurgy such as metal in-jection molding(MIM).In this study,we purposely selected the Ti and Ti-6Al-4V powders as the reference materials since these two are the most representative Ti materials in the industry.Herein,hydride-dehydride(HDH)Ti powders were pre-oxidized to examine the ef-fect of oxygen variation on the characteristics of oxide layer on the particle surface and its resultant color feature.The results indicate that the thickness and Ti oxide level(Ti^(0)→Ti^(4+))of the oxide layer on the HDH Ti powders increased as the oxygen content increased,lead-ing to the transition of color appearance from grey,brown to blue.This work aids in the powder feedstock selection at the initial stage in powder metallurgy.In addition,the development of oxygen content was comprehensively studied during the MIM process using the gas-atomized(GA)Ti-6Al-4V powders.Particularly,the oxygen variation in the form of oxide layer,the change of oxygen content in the powders,and the relevant parts were investigated during the processes of kneading,injection,debinding,and sintering.The oxygen vari-ation was mainly concentrated in the sintering stage,and the content increased with the increase of sintering temperature.The variation of oxygen content during the MIM process demonstrates the crucial role of powder feedstock and sintering stage in controlling oxygen con-tent.This work provides a piece of valuable information on oxygen detecting,control,and manipulation for the powder and processing in the industry of Ti and its alloys by powder metallurgy.

Intravitreal injection practice patterns among Chinese ophthalmologists

AIM:To describe the practice patterns of intravitreal injections(IVIs)among ophthalmologists in China.METHODS:This was a cross-sectional online survey.Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center,a hospital-based national network,to complete an anonymous,24-question,internet-based survey.They were surveyed on practices in injection techniques,pre-,and post-injections procedures.RESULTS:A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey(50.68%response rate).The 91.29%of the respondents evaluated systemic risk factors by medical history,electrocardiogram(ECG)and blood test.All the respondents used pre-injection prophylactic antibiotics.Most checked intraocular pressure(IOP,99.1%)and blood pressure(96.1%)before injections.A majority of the respondents performed injections in the operating room(98.8%),wore masks(99.7%),gloves(99.4%)and sterile surgical clothing(96.1%),performed topical anesthetics(97.9%),and applied povidone-iodine(95.8%)pre-injection.The 61.26%of the respondents dilated pupil.About half of the respondents(51.05%)performed bilateral injections in the same setting.Superior temporal quadrant(40.54%)was the most frequent site of injection.Around three quarters used 30-gauge needles.Most respondents(97.9%)measured the site of injection from limbus.More than half(53.45%)performed conjunctiva displacement prior to injection.The 32.43%of the respondents checked IOP post-injection and 87.99%physicians checked hand motion(HM)or counting fingers(CF)after injection,while 36.94%observed optic nerve perfusion.All participants used topical antibiotics post-injections.Most physicians(91.89%)reviewed patients on the following day.CONCLUSION:This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Modeling injection-induced fault slip using long short-term memory networks

Stress changes due to changes in fluid pressure and temperature in a faulted formation may lead to the opening/shearing of the fault.This can be due to subsurface(geo)engineering activities such as fluid injections and geologic disposal of nuclear waste.Such activities are expected to rise in the future making it necessary to assess their short-and long-term safety.Here,a new machine learning(ML)approach to model pore pressure and fault displacements in response to high-pressure fluid injection cycles is developed.The focus is on fault behavior near the injection borehole.To capture the temporal dependencies in the data,long short-term memory(LSTM)networks are utilized.To prevent error accumulation within the forecast window,four critical measures to train a robust LSTM model for predicting fault response are highlighted:(i)setting an appropriate value of LSTM lag,(ii)calibrating the LSTM cell dimension,(iii)learning rate reduction during weight optimization,and(iv)not adopting an independent injection cycle as a validation set.Several numerical experiments were conducted,which demonstrated that the ML model can capture peaks in pressure and associated fault displacement that accompany an increase in fluid injection.The model also captured the decay in pressure and displacement during the injection shut-in period.Further,the ability of an ML model to highlight key changes in fault hydromechanical activation processes was investigated,which shows that ML can be used to monitor risk of fault activation and leakage during high pressure fluid injections.

Mechanistic investigation of gas injection treatment in a continental shale gas condensate reservoir

Low thermal evolution degree of gas and connected fracture network are key features in the continental shale gas reservoirs.When the pressure decreases lower than the dew point pressure,gas condensate diminishes the mobility of subsurface fluid forms in the near well region,which further reduces the productivity and final recovery factor in addition to the low connected fracture network.This work is motivated to investigate the application of gas injection,proven to be a feasible technique in conventional/marine-shale gas condensate reservoirs,in continental shale gas condensate reservoirs.We apply a compositional model to investigate the mechanism of gas injection treatment taking a continental shale gas condensate reservoir in the Fuxing area,Sichuan Basin,China as an example.The results demonstrate that for the removal of gas condensate during CO_(2)injection,re-vaporization plays the main mechanism through two processes including pressurization and development of miscibility,while the former is overwhelming.Considering the variation trend of the total volume of gas condensate,we divide the whole injection process into four and six stages in the single fracture model and fracture network model,respectively,and reason the trend with respect to phase behavior and flow pattern.A sensitive study on the injected gas type indicates that the sorting of the gas injection performance to remove gas condensate produced gas followed by CH4,and followed by CO_(2).Finally,we investigate the performance of cyclic produced-gas injection and optimize the injection scheme.This work provides technical and theoretical support for the development of continental shale gas reservoirs.

Cross-upgrading of biomass hydrothermal carbonization and pyrolysis for high quality blast furnace injection fuel production:Physicochemical characteristics and gasification kinetics analysis

The paper proposes a biomass cross-upgrading process that combines hydrothermal carbonization and pyrolysis to produce high-quality blast furnace injection fuel.The results showed that after upgrading,the volatile content of biochar ranged from 16.19%to 45.35%,and the alkali metal content,ash content,and specific surface area were significantly reduced.The optimal route for biochar pro-duction is hydrothermal carbonization-pyrolysis(P-HC),resulting in biochar with a higher calorific value,C=C structure,and increased graphitization degree.The apparent activation energy(E)of the sample ranges from 199.1 to 324.8 kJ/mol,with P-HC having an E of 277.8 kJ/mol,lower than that of raw biomass,primary biochar,and anthracite.This makes P-HC more suitable for blast furnace injection fuel.Additionally,the paper proposes a path for P-HC injection in blast furnaces and calculates potential environmental benefits.P-HC of-fers the highest potential for carbon emission reduction,capable of reducing emissions by 96.04 kg/t when replacing 40wt%coal injec-tion.

Efficacy of acupoint injection in the treatment of chronic eczema and its influence on peripheral blood T cells

BACKGROUND Chronic eczema significantly impacts daily life,social interactions,and quality of life;however,no curative treatment has been identified.AIM To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells.METHODS Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group(n=40),which received conventional Western medicine treatment,or an observation group(n=40),which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide.Response and adverse reaction rates,as well as differences in the levels of serum cytokines IFN-γ,IL-2,IL-4,and IL-10 before and after treatment were investigated.RESULTS No difference in overall response rates were found between the observation and control groups(100%vs 90%,respectively;P>0.05);however,the observation group had a higher marked response rate than the control group(87.5%vs 52.5%;P<0.05).Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment(P<0.05),particularly in the observation group(P<0.05).The observation group had an adverse reaction rate of 2.5%(1/40),which did not differ significantly from that of the control group(P>0.05).The observation group exhibited higher post-treatment INF-γand IL-2 but lower IL-4 levels than the control group(P<0.05);however,no significant inter-group difference was observed in post-treatment IL-10 levels(P>0.05).CONCLUSION Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema.Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels,inhibition of inflammatory reactions,and mitigation of immune imbalance.

Self-expanding metal stent for relieving the stricture after endoscopic injection for esophageal varices

BACKGROUND Esophageal stricture is one of the complications after esophageal varices sclero-therapy injection(ESI),and the incidence rate is between 2%-10%.AIM To explore the efficacy of self-expanding metal stent(SEMS)for the stricture after endoscopic injection with cyanoacrylate(CYA)and sclerotherapy for esophageal varices.METHODS We retrospectively analyzed the efficacy of SEMS to improve the stricture after endoscopic injection with CYA and sclerotherapy for esophageal varices in 4 patients from February 2023 to June 2023.RESULTS The strictures were improved in four patients after stenting.The stent was removed after two weeks because of chest pain with embedding into esophageal mucosa in one patient.The stent was removed after one month,however,the stent was reinserted because of the strictures happening again in two patients.The stent was removed after three months,however,the stent was reinserted because of the strictures happening again in one patient.The stent embedded into esophageal mucosa in three patients.There were 3 patients suffered reflux esophagitis,and the acid reflux was relieved by taking hydrotalcite.There was no other complication of esophageal perforation,bleeding from varices or infection.CONCLUSION SEMS may relieve the stricture which happened after endoscopic injection with CYA and sclerotherapy for esophageal varices.However,when we should remove the stent still needs to be explored.

Horizontal well spacing optimization and gas injection simulation for the ultra-low-permeability Yongjin reservoir

Optimal spacing for vertical wells can be effectively predicted with several published methods,but methods suitable for assessing the proper horizontal well spacing are rare.This work proposes a method for calculating the optimal horizontal well spacing for an ultra-low permeability reservoir e the Yongjin reservoir in the Juggar Basin,northwestern China.The result shows that a spacing of 640m is the most economical for the development of the reservoir.To better develop the reservoir,simulation approaches are used and a new model is built based on the calculated well spacing.Since the reservoir has an ultralow permeability,gas injection is regarded as the preferred enhanced oil recovery(EOR)method.Injection of different gases including carbon dioxide,methane,nitrogen and mixed gas are modelled.The results show that carbon dioxide injection is the most efficient and economical for the development of the reservoir.However,if the reservoir produces enough methane,reinjecting methane is even better than injecting carbon dioxide.